51. Synthesis and biological evaluation of a series of aromatic bisphosphonates
- Author
-
Rocky J. Barney, David F. Wiemer, Raymond J. Hohl, Amel Dudakovic, and Brian M. Wasko
- Subjects
Stereochemistry ,medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Biochemistry ,Farnesyl diphosphate synthase ,Prenylation ,Cell Line, Tumor ,Drug Discovery ,medicine ,Farnesyltranstransferase ,Humans ,Enzyme Inhibitors ,Molecular Biology ,Binding Sites ,Diphosphonates ,biology ,Chemistry ,organic chemicals ,Organic Chemistry ,Geranyltranstransferase ,Biological activity ,Bisphosphonate ,body regions ,Enzyme inhibitor ,biology.protein ,Molecular Medicine ,Protein prenylation ,lipids (amino acids, peptides, and proteins) - Abstract
Geminal bisphosphonates display varied biological activity depending on the nature of the substituents on the central carbon atom. For example, the nitrogenous bisphosphonates zoledronate and risedronate inhibit the enzyme farnesyl diphosphate synthase while digeranyl bisphosphonate has been shown to inhibit the enzyme geranylgeranyl diphosphate synthase. We now have synthesized isoprenoid bisphosphonates where an aromatic ring has been used to replace one of the isoprenoid olefins in an isoprenoid bisphosphonate and investigated the ability of these new compounds to impair protein geranylgeranylation within cells. Several of these new compounds are potent inhibitors of the enzyme geranylgeranyl diphosphate synthase.
- Published
- 2010